Modern-day stenting procedures leverage advances in pharmacotherapy and device innovation. Patients treated with contemporary antiplatelet agents, peri-procedural antithrombin therapy and ...new-generation drug-eluting stents (DES) have excellent outcomes over the short to medium term. Indeed, coupled with the reducing costs of these devices in most countries there remain very few indications where patients should be denied treatment with standard-of-care DES therapy. The two major causes of stent failure are stent thrombosis (ST) and in-stent restenosis (ISR). The incidence of both has reduced considerably in recent years. Current clinical registries and randomized trials with broad inclusion criteria show rates of ST at or <1% after 1 year and ∼0.2-0.4% per year thereafter; rates of clinical ISR are 5% respectively. Angiographic surveillance studies in large cohorts show rates of angiographic ISR of ∼10% with new-generation DES. The advent of high-resolution intracoronary imaging has shown that in many cases of late stent failure neoatherosclerotic change within the stented segment represents a final common pathway for both thrombotic and restenotic events. In future, a better understanding of the pathogenesis of this process may translate into improved late outcomes. Moreover, the predominance of non-stent-related disease as a cause of subsequent myocardial infarction during follow-up highlights the importance of lifestyle and pharmacological interventions targeted at modification of the underlying disease process. Finally, although recent developments focus on strategies which circumvent the need for chronically indwelling stents--such as drug-coated balloons or fully bioresorbable stents-more data are needed before the wider use of these therapies can be advocated.
Gamma-glutamyl transferase (GGT) is a ubiquitous cell surface enzyme that cleaves extracellular glutathione (G-SH) or other gamma-glutamyl compounds. GGT serves to increase the availability of amino ...acids, primarily cysteine, for intracellular G-SH synthesis and plays a crucial role in maintaining G-SH homeostasis and defense against oxidative stress in organisms. Measurement of circulating GGT activity is widely used for the diagnosis of liver and obstructive biliary diseases and as an indicator of alcohol consumption. Epidemiological studies suggest an association between elevated GGT activity level and a risk of incident coronary heart disease (CHD) or CHD-related mortality. Elevated GGT activity level is associated with a plethora of cardio-metabolic risk factors, including traditional cardiovascular risk factors, metabolic syndrome, systemic inflammation, oxidative stress burden and various comorbidities that incur a negative impact on patient risk profile and prognosis. Experimental studies and studies of human atherosclerotic plaques have revealed not only the presence of catalytically active GGT in atherosclerotic plaques, but also a correlation between GGT activity and indices of plaque instability, suggesting direct involvement in the pathophysiology of atherosclerosis and related clinical events via promotion of pro-oxidant reactions by the enzyme. However, it remains unknown whether GGT plays a direct role in the pathophysiology of atherosclerosis and CHD or is merely a correlate of coexisting cardiovascular risk factors. The exact molecular mechanisms of GGT participation in atherosclerosis or CHD and assessment of GGT-lowering therapies, as well as their impact on clinical outcomes, remain to be investigated in longitudinal studies.
•Gamma-glutamyl transferase (GGT) activity is associated with the risk of incident coronary heart disease.•GGT activity is associated with the risk of all-cause and cardiovascular mortality.•Elevated GGT activity correlates with cardiovascular risk factors and signifies an increased cardiovascular risk.•GGT is present in atherosclerotic plaques and correlates with indices of plaque instability.
Current Treatment of In-Stent Restenosis Alfonso, Fernando, MD, PhD; Byrne, Robert A., MB, BCh, PhD; Rivero, Fernando, MD ...
Journal of the American College of Cardiology,
06/2014, Letnik:
63, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Management of patients with in-stent restenosis (ISR) remains an important clinical problem. Although drug-eluting stents (DES) have drastically reduced the incidence of ISR, treatment of DES-ISR is ...particularly challenging. ISR mainly results from aggressive neointimal proliferation, but recent data also suggest that neoatherosclerosis may play an important pathophysiological role. Intracoronary imaging provides unique insights to unravel the underlying substrate of ISR and may be used to guide repeated interventions. In this paper, we systematically reviewed clinical trial data with currently available therapeutic modalities, including DES and drug-coated balloons, in patients presenting with ISR within bare-metal stents or DES.
Summary Background Percutaneous coronary intervention (PCI) with drug-eluting stents is the standard of care for treatment of native coronary artery stenoses, but optimum treatment strategies for ...bare metal stent and drug-eluting stent in-stent restenosis (ISR) have not been established. We aimed to compare and rank percutaneous treatment strategies for ISR. Methods We did a network meta-analysis to synthesise both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomised controlled trials published up to Oct 31, 2014, of different PCI strategies for treatment of any type of coronary ISR. The primary outcome was percent diameter stenosis at angiographic follow-up. This study is registered with PROSPERO, number CRD42014014191. Findings We deemed 27 trials eligible, including 5923 patients, with follow-up ranging from 6 months to 60 months after the index intervention. Angiographic follow-up was available for 4975 (84%) of 5923 patients 6–12 months after the intervention. PCI with everolimus-eluting stents was the most effective treatment for percent diameter stenosis, with a difference of −9·0% (95% CI −15·8 to −2·2) versus drug-coated balloons (DCB), −9·4% (–17·4 to −1·4) versus sirolimus-eluting stents, −10·2% (–18·4 to −2·0) versus paclitaxel-eluting stents, −19·2% (–28·2 to −10·4) versus vascular brachytherapy, −23·4% (–36·2 to −10·8) versus bare metal stents, −24·2% (–32·2 to −16·4) versus balloon angioplasty, and −31·8% (–44·8 to −18·6) versus rotablation. DCB were ranked as the second most effective treatment, but without significant differences from sirolimus-eluting (–0·2% 95% CI −6·2 to 5·6) or paclitaxel-eluting (–1·2% –6·4 to 4·2) stents. Interpretation These findings suggest that two strategies should be considered for treatment of any type of coronary ISR: PCI with everolimus-eluting stents because of the best angiographic and clinical outcomes, and DCB because of its ability to provide favourable results without adding a new stent layer. Funding None.
Summary Background Bioresorbable coronary stents might improve outcomes of patients treated with percutaneous coronary interventions. The everolimus-eluting bioresorbable vascular scaffold is the ...most studied of these stent platforms; however, its performance versus everolimus-eluting metallic stents remains poorly defined. We aimed to assess the efficacy and safety of everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents in patients with ischaemic heart disease treated with percutaneous revascularisation. Methods We searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), scientific sessions abstracts, and relevant websites for randomised trials investigating everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents published or posted between Nov 30, 2006, and Oct 12, 2015. The primary efficacy outcome was target lesion revascularisation and the primary safety outcome was definite or probable stent (scaffold) thrombosis. Secondary outcomes were target lesion failure (the composite of cardiac death, target-vessel myocardial infarction, or ischaemia-driven target lesion revascularisation), myocardial infarction, death, and in-device late lumen loss. We derived odds ratios (ORs) and weighted mean differences with 95% CIs, and calculated the risk estimates for the main outcomes according to a random-effects model. This study is registered with PROSPERO, number CRD42015026374. Findings We included six trials, comprising data for 3738 patients randomised to receive percutaneous coronary intervention with either an everolimus-eluting bioresorbable vascular scaffold (n=2337) or an everolimus-eluting metallic stent (n=1401). Median follow-up was 12 months (IQR 9–12). Patients treated with bioresorbable vascular scaffolds had a similar risk of target lesion revascularisation (OR 0·97 95% CI 0·66–1·43; p=0·87), target lesion failure (1·20 0·90–1·60; p=0·21), myocardial infarction (1·36 0·98–1·89; p=0·06), and death (0·95 0·45–2·00; p=0·89) as those treated with metallic stents. Patients treated with a bioresorbable vascular scaffold had a higher risk of definite or probable stent thrombosis than those treated with a metallic stent (OR 1·99 95% CI 1·00–3·98; p=0·05), with the highest risk between 1 and 30 days after implantation (3·11 1·24–7·82; p=0·02). Lesions treated with a bioresorbable vascular scaffold had greater in-device late lumen loss than those treated with a metallic stent (weighted mean difference 0·08 95% CI 0·05–0·12; p<0·0001). Interpretation Compared with everolimus-eluting metallic stents, everolimus-eluting bioresorbable vascular scaffolds had similar rates of repeat revascularisation at 1 year of follow-up, despite inferior mid-term angiographic performance. However, patients treated with a bioresorbable vascular scaffold had an increased risk of subacute stent thrombosis. Studies with extended follow-up in a larger number of patients are needed to fully assess the long-term advantages of everolimus-eluting bioresorbable vascular scaffolds. Funding None.
Despite the reduction in late thrombotic events with newer-generation drug-eluting stents (DES), late stent failure remains a concern following stent placement. In-stent neoatherosclerosis has ...emerged as an important contributing factor to late vascular complications including very late stent thrombosis and late in-stent restenosis. Histologically, neoatherosclerosis is characterized by accumulation of lipid-laden foamy macrophages within the neointima with or without necrotic core formation and/or calcification. The development of neoatherosclerosis may occur in months to years following stent placement, whereas atherosclerosis in native coronary arteries develops over decades. Pathologic and clinical imaging studies have demonstrated that neoatherosclerosis occurs more frequently and at an earlier time point in DES when compared with bare metal stents, and increases with time in both types of implant. Early development of neoatherosclerosis has been identified not only in first-generation DES but also in second-generation DES. The mechanisms underlying the rapid development of neoatherosclerosis remain unknown; however, either absence or abnormal endothelial functional integrity following stent implantation may contribute to this process. In-stent plaque rupture likely accounts for most thrombotic events associated with neoatherosclerosis, while it may also be a substrate of in-stent restenosis as thrombosis may occur either symptomatically or asymptomatically. Intravascular optical coherence tomography is capable of detecting neoatherosclerosis; however, the shortcomings of this modality must be recognized. Future studies should assess the impact of iterations in stent technology and risk factor modification on disease progression. Similarly, refinements in imaging techniques are also warranted that will permit more reliable detection of neoatherosclerosis.
Objectives The aim of this study was to test whether the left ventricular assist device (LVAD) Impella LP2.5 (Abiomed Europe GmbH, Aachen, Germany) provides superior hemodynamic support compared with ...the intra-aortic balloon pump (IABP). Background Cardiogenic shock caused by left ventricular failure is associated with high mortality in patients with acute myocardial infarction (AMI). An LVAD may help to bridge patients to recovery from left ventricular failure. Methods In a prospective, randomized study, 26 patients with cardiogenic shock were studied. The primary end point was the change of the cardiac index (CI) from baseline to 30 min after implantation. Secondary end points included lactic acidosis, hemolysis, and mortality after 30 days. Results In 25 patients the allocated device (n = 13 IABP, n = 12 Impella LP2.5) could be safely placed. One patient died before implantation. The CI after 30 min of support was significantly increased in patients with the Impella LP2.5 compared with patients with IABP (Impella: ΔCI = 0.49 ± 0.46 l/min/m2 ; IABP: ΔCI = 0.11 ± 0.31 l/min/m2 ; p = 0.02). Overall 30-day mortality was 46% in both groups. Conclusions In patients presenting with cardiogenic shock caused by AMI, the use of a percutaneously placed LVAD (Impella LP 2.5) is feasible and safe, and provides superior hemodynamic support compared with standard treatment using an intra-aortic balloon pump. (Efficacy Study of LV Assist Device to Treat Patients With Cardiogenic Shock ISAR-SHOCK; NCT00417378 )
Nonstent-based local drug delivery during percutaneous intervention offers potential for sustained antirestenotic efficacy without the limitations of permanent vascular implants. Preclinical studies ...have shown that effective local tissue concentrations of drugs can be achieved using drug-coated balloon (DCB) catheters. Matrix coatings consisting of a mixture of lipophilic paclitaxel and hydrophilic spacer (excipient) are most effective. Clinical applications most suited to DCB therapy are those for which stent implantation is not desirable or less effective, such as in-stent restenosis, bifurcation lesions, or peripheral artery stenoses. Randomized trials have shown superiority of DCBs over plain-balloon angioplasty for both bare-metal and drug-eluting coronary in-stent restenosis, and similar efficacy as repeat stenting with a drug-eluting stent (DES). Bycontrast, randomized trials of DCBs in de novo coronary stenosis have, to date, not shown similar efficacy to standard-of-care DES therapy. In peripheral artery disease, DCB therapy has proven superior to plain-balloon angioplasty for treatment of de novo femoropoliteal and below-the-knee disease, and shown promising results for in-stent restenosis. Overall, however, despite many years of clinical experience with DCBs, the number of large, high-quality, randomized clinical trials is low, and further data are urgently needed across the spectrum of clinical indications.
PDF
